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GCLM glutamate-cysteine ligase modifier subunit [ Homo sapiens (human) ]

Gene ID: 2730, updated on 13-Feb-2019

Summary

Official Symbol
GCLMprovided by HGNC
Official Full Name
glutamate-cysteine ligase modifier subunitprovided by HGNC
Primary source
HGNC:HGNC:4312
See related
Ensembl:ENSG00000023909 MIM:601176
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GLCLR
Summary
Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase, is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Expression
Ubiquitous expression in liver (RPKM 13.0), thyroid (RPKM 9.9) and 24 other tissues See more
Orthologs

Genomic context

See GCLM in Genome Data Viewer
Location:
1p22.1
Exon count:
9
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 1 NC_000001.11 (93885199..93910370, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (94352590..94375154, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene transfer RNA-Arg (TCT) 1-1 Neighboring gene deoxynucleotidyltransferase terminal interacting protein 2 Neighboring gene coiled-coil-helix-coiled-coil-helix domain containing 2 pseudogene 5 Neighboring gene MT-ND4 pseudogene 11

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Myocardial infarction 1
MedGen: C1832662 OMIM: 608446 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of glutamate-cysteine ligase, modifier subunit (GCLM) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enzyme regulator activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to glutamate-cysteine ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to glutamate-cysteine ligase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
glutamate-cysteine ligase catalytic subunit binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IEA
Inferred from Electronic Annotation
more info
 
Process Evidence Code Pubs
aging IEA
Inferred from Electronic Annotation
more info
 
apoptotic mitochondrial changes IEA
Inferred from Electronic Annotation
more info
 
cellular response to fibroblast growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to follicle-stimulating hormone stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to hepatocyte growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to leukemia inhibitory factor IEA
Inferred from Electronic Annotation
more info
 
cellular response to thyroxine stimulus IEA
Inferred from Electronic Annotation
more info
 
cysteine metabolic process IEA
Inferred from Electronic Annotation
more info
 
glutamate metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
glutathione biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutathione biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
glutathione biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
glutathione biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
glutathione biosynthetic process TAS
Traceable Author Statement
more info
 
hepatic stellate cell activation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of extrinsic apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of glutamate-cysteine ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of blood vessel size IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of mitochondrial depolarization IEA
Inferred from Electronic Annotation
more info
 
response to activity IEA
Inferred from Electronic Annotation
more info
 
response to drug IDA
Inferred from Direct Assay
more info
PubMed 
response to human chorionic gonadotropin IEA
Inferred from Electronic Annotation
more info
 
response to nitrosative stress IEA
Inferred from Electronic Annotation
more info
 
response to nutrient IEA
Inferred from Electronic Annotation
more info
 
response to oxidative stress IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
cytosol NAS
Non-traceable Author Statement
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
glutamate-cysteine ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutamate-cysteine ligase complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
glutamate--cysteine ligase regulatory subunit
Names
GCS light chain
GSC light chain
gamma-ECS regulatory subunit
gamma-glutamylcysteine synthetase regulatory subunit
glutamate-cysteine ligase (gamma-glutamylcysteine synthetase), regulatory (30.8kD)
glutamate-cysteine ligase modifier subunit delta2 alternative splicing
glutamate-cysteine ligase regulatory protein
NP_001295182.1
NP_002052.1
XP_011539563.1
XP_016856545.1
XP_016856546.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012072.1 RefSeqGene

    Range
    4859..29258
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001308253.1NP_001295182.1  glutamate--cysteine ligase regulatory subunit isoform 2

    See identical proteins and their annotated locations for NP_001295182.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 2 which has the same N- and C-termini, but is shorter than isoform 1.
    Source sequence(s)
    AB809606, AK290449, BC041809, BF513627, BG501583, BM982562, BQ049850, BU754400, CB123306, CN272168, CN422503, N53134
    Consensus CDS
    CCDS81352.1
    UniProtKB/Swiss-Prot
    P48507
    Related
    ENSP00000484507.1, ENST00000615724.1
    Conserved Domains (1) summary
    cl00470
    Location:95189
    Aldo_ket_red; Aldo-keto reductases (AKRs) are a superfamily of soluble NAD(P)(H) oxidoreductases whose chief purpose is to reduce aldehydes and ketones to primary and secondary alcohols. AKRs are present in all phyla and are of importance to both health and industrial ...
  2. NM_002061.4NP_002052.1  glutamate--cysteine ligase regulatory subunit isoform 1

    See identical proteins and their annotated locations for NP_002052.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AK290449, BC041809, BF513627, BM982562, BQ049850, BU754400, CB123306, CN272168, CN422503, N53134
    Consensus CDS
    CCDS746.1
    UniProtKB/Swiss-Prot
    P48507
    Related
    ENSP00000359258.3, ENST00000370238.7
    Conserved Domains (1) summary
    cl00470
    Location:117211
    Aldo_ket_red; Aldo-keto reductases (AKRs) are a superfamily of soluble NAD(P)(H) oxidoreductases whose chief purpose is to reduce aldehydes and ketones to primary and secondary alcohols. AKRs are present in all phyla and are of importance to both health and industrial ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 Primary Assembly

    Range
    93885199..93910370 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017001057.2XP_016856546.1  glutamate--cysteine ligase regulatory subunit isoform X2

  2. XM_017001056.2XP_016856545.1  glutamate--cysteine ligase regulatory subunit isoform X1

  3. XM_011541261.2XP_011539563.1  glutamate--cysteine ligase regulatory subunit isoform X3

    Conserved Domains (1) summary
    cl00470
    Location:29123
    Aldo_ket_red; Aldo-keto reductases (AKRs) are a superfamily of soluble NAD(P)(H) oxidoreductases whose chief purpose is to reduce aldehydes and ketones to primary and secondary alcohols. AKRs are present in all phyla and are of importance to both health and industrial ...
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